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Biomedical subjects

A Meissner

Publications and source records attributed to A Meissner.

At least 19 recordsLinked to original sources

13C natural abundance S3E and S3CT experiments for measurement of J coupling constants between 13Calpha or 1Halpha and other protons in a protein.

It is demonstrated that the spin-state-selective pulse sequence elements, S3E and S3CT, previously introduced for measurement of J coupling constants in 15N-labeled proteins can be applied for work with peptides and proteins with 13C at the natural abundance level. In addition, a method is described for suppression of crosstalk caused by passive spin flips and pulse imperfections, which otherwise results in systematically underestimated J coupling constants and thereby inaccurate structural constraints. This method is also applicable for crosstalk suppression in applications of S3E and S3CT to 13C- or 15N-labeled samples. Experimental confirmation is obtained using a 10 mM BPTI sample focusing on 13C in the alpha position. The measured J coupling constants include 3J(HN-Halpha) and 3J(Halpha-Hbeta) related to the phi and chi1 angles, respectively.

Carbon Isotopes

High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting.

UNLABELLED: In this prospective study, we evaluated whether high thoracic epidural anesthesia (TEA) or i.v. clonidine, in addition to general anesthesia, affects the cardiopulmonary bypass- and surgery-associated stress response and incidence of myocardial ischemia by their sympatholytic properties. Seventy patients scheduled for elective coronary artery bypass graft (CABG) received general anesthesia with sufentanil and propofol. TEA was randomly induced before general anesthesia and continued during the study period in 25 (anesthetized dermatomes C6-T10). Another 24 patients received i.v. clonidine as a bolus of 4 microg/kg before the induction of general anesthesia. Clonidine was then infused at a rate of 1 microg x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1) postoperatively. The remaining 21 patients underwent general anesthesia as performed routinely (control). Hemodynamics, plasma epinephrine and norepinephrine, cortisol, the myocardial-specific contractile protein troponin T, and other cardiac enzymes were measured pre- and postoperatively. During the preoperative night and a follow-up of 48 h after surgery, five-lead electrocardiogram monitoring was used for ischemia detection. Both TEA and clonidine reduced the postoperative heart rate compared with the control group without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine increased perioperatively in all groups but was significantly lower in the TEA group. Neither TEA nor clonidine affected the increase in plasma cortisol. The release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or new ST depression > or = 0.1 mV occurred in > 70% of the control patients but only in 40% of the clonidine group and in 50% of the TEA group. We conclude that TEA (but not i.v. clonidine) combined with general anesthesia for CABG demonstrates a beneficial effect on the perioperative stress response and postoperative myocardial ischemia. IMPLICATIONS: Thoracic epidural anesthesia combined with general anesthesia attenuates the myocardial sympathetic response to cardiopulmonary bypass and cardiac surgery. This is associated with decreased myocardial ischemia as determined by less release of troponin T. These findings may have an impact on the anesthetic management for coronary artery bypass grafting.

Adrenergic alpha-Agonists

Inotropic effects of diadenosine tetraphosphate in isolated canine cardiac preparations.

We studied the effects of diadenosine tetraphosphate (AP4A) on the force of contraction in canine preparations. The force of contraction was measured in isolated electrically driven (1 Hz) atrial and ventricular cardiac trabeculae from adult dogs. AP4A (100 microM) alone and after prestimulation with 10 nM isoproterenol reduced force of contraction in atrial preparations by approximately 24%. Moreover, AP4A (100 microM) alone and after prestimulation with 10 nM isoproterenol reduced the force of contraction in ventricular preparations by 29 and 29%, respectively. The negative inotropic effects of AP4A were abolished by the A1-adenosine receptor antagonist 1,3-dipropyl-cyclopentyl-xanthine (DPCPX). In summary, in canine myocardium, AP4A alone and after prestimulation with a beta-adrenoceptor agonist exerts negative inotropic effects, which are probably mediated via A1-adenosine receptors.

Animals

Effects of angiotensin II on inotropy and intracellular Ca2+ handling in normal and hypertrophied rat myocardium.

The direct inotropic effect of angiotensin II on the myocardium is still controversial and little information exists as to its potential modification by heart disorders. Therefore, this study performed simultaneous measurements of isometric force and intracellular Ca2+ concentrations ([Ca2+]i) in left ventricular papillary muscles from sham-operated and aortic-banded rats at 10 weeks post-surgery. Angiotensin II (10(-6) M) induced a reduction of peak systolic [Ca2+]i (0.56 +/- 0.03 to 0.48 +/- 0.04 microM; P<0.05) and a parallel but insignificant diminution of developed tension (10.5 +/- 1.3 to 9.6 +/- 0.8 mN/mm2) in normal papillary muscles from sham-operated animals. Hypertrophied papillary muscles from aortic-banded rats demonstrated a significant decline in both peak systolic [Ca2+]i (0.51 +/- 0.02 to 0.44 +/- 0.01 microM; P<0.05) and developed tension (8.4 +/- 1.1 to 6.8 +/- 1.7 mN/mm2; P<0.05) after addition of angiotensin II. The time courses of the mechanical contraction and the intracellular Ca2+ signal were prolonged by angiotension II in both groups. Isoproterenol dose-dependently increased developed tension and peak systolic [Ca2+]i in papillary muscles from sham-operated rats. In contrast, the positive inotropic response to isoproterenol was markedly reduced in hypertrophied muscles despite a seemingly unimpaired increase in peak systolic [Ca2+]i. Pretreatment with angiotensin II (10(-6) M) resulted in a significant attenuation of the systolic [Ca2+]i response to isoproterenol stimulation in both normal and hypertrophied papillary muscles. Neither the bradykinin B2 antagonist icatibent (10(-6) M) nor the nitric oxide (NO) inhibitor L-NMMA (10(-6) M) abolished the depressant effects of angiotension II. Thus, ANG II induces a parallel decline of the mechanical performance and Ca2+ availability in rat myocardium. These effects are more distinct in hypertrophied than in normal muscle and become accentuated during beta-adrenergic stimulation. The underlying mechanism is not associated with the NO pathway but might involve a negative functional coupling between the angiotensin and beta-adrenergic-receptor complex.

Angiotensin II

New multidimensional editing experiments for measurement of amide deuterium isotope effects on Cbeta chemical shifts in 13C, 15N-labeled proteins.

Novel multidimensional NMR pulse sequences for measurement of the three- and four-bond amide deuterium isotope effect on the chemical shifts of 13Cbeta in proteins are presented. The sequences result in editing into two subspectra of a heteronuclear triple resonance spectrum ¿omega(N), omega(Cbeta), omega(Halpha)¿ according to there being a deuterium or a proton attached to 15N for the pertinent correlations. The new experiments are demonstrated by an application to the first module of the 13C,15N-labeled protein RAP 18-112 (N-terminal module of alpha2-macroglobulin receptor associated protein).

Amides

[Comparison of internal fixation methods for the symphysis in multi-directional dynamic gait simulation].

For the stabilization of the ruptured pubic symphysis, rigid forms of fixation such as plate osteosynthesis and flexible fixations such as wire loops or PDS banding have been recommended. All methods have only been tested by static unidirectional loading until failure of the system. By this experimental arrangement Ecke and Hofmann found comparable results for flexible and rigid methods of internal stabilization of the pubic symphysis. They preferred flexible methods to maintain mobility of the symphysis and to prevent symphyseal fusion. We tested dynamic compression plate osteosynthesis, reconstruction plate osteosynthesis, wire loops and PDS banding for internal fixation of injured pubic symphysis in a dynamic multidirectional experimental arrangement simulating gait conditions. The specimens were loaded with 85 N in vertical (y-) direction and 34 N in sagittal (z-) direction, which represent 50% of the forces acting at the pubic symphysis during walking and with a frequency of 1.5 Hz over 55,500 loads simulating the conditions over a 6-week mobilization period. Loading with 100% of the acting forces (corresponding to full weight bearing mobilization) led to early failure of the system. Our experimental analysis showed that neither wire loops nor PDS banding is able to stabilize the ruptured pubic symphysis, even immediately after fixation before loading. During the tests instability increased until failure of the system due to cutting of the bone or breaking of the wires or PDS banding. Success of plate osteosynthesis was dependent on the initial stability of the fixation. Overwinding of the screws, as in osteoporotic bone, lead to increasing loosening during repeated loading, whereas primary stable fixation of the screws was almost completely maintained during the test. In consequence, neither wire loops nor PDS banding should be used for stabilization of injured pubic symphysis if early mobilization with partial weight bearing is desired. Plate osteosynthesis (DC or reconstruction plate) tolerates early half weight bearing in patients with "open-book" injury only if safe screw fixation is guaranteed.

Biomechanical Phenomena

Thoracic epidural anesthesia does not affect functional recovery from myocardial stunning in sevoflurane-anesthetized dogs.

OBJECTIVE: A beneficial effect of thoracic epidural anesthesia (TEA) on recovery from myocardial stunning was previously shown in awake dogs. The aim of this study was to investigate the effects of TEA on recovery from myocardial stunning in sevoflurane-anesthetized dogs. DESIGN: Randomized animal study. SETTING: Animal laboratory of a university hospital. PARTICIPANTS: Chronically instrumented mongrel dogs. INTERVENTIONS: Six dogs were chronically instrumented for measurement of hemodynamics and myocardial wall thickening fraction (WTF). The following experiments were performed on separate days in a crossover fashion: (1) 10 minutes of ischemia of the left anterior descending (LAD) coronary artery during sevoflurane anesthesia without TEA and (2) 10 minutes of ischemia during sevoflurane anesthesia with TEA. MEASUREMENTS AND MAIN RESULTS: WTF was measured awake (baseline) and at predetermined time points until complete recovery of myocardial function occurred. Induction of anesthesia led to a decrease of WTF compared with baseline. Induction of ischemia led to a further decrease of WTF to negative values, which returned to positive values within the first minute of reperfusion. There were no differences between the two experimental conditions at any of the time points measured. In awake dogs, TEA improved the recovery from myocardial stunning compared with the control experiment. There was no difference between conscious dogs with TEA or sevoflurane-anesthetized dogs with or without TEA. CONCLUSION: TEA has no additional protective effect on the recovery of WTF during sevoflurane anesthesia.

Anesthesia, Epidural

[Rehabilitation of psychiatric patients by half-way house admission--a catamnestic study].

In order to observe the course of rehabilitation of mentally ill persons a catamnestic study was done of 16 mainly schizophrenic former residents of the halfway house for mentally ill in Nuremberg. Along with the rehospitalization rate, the criteria for success were progress in the living and working fields. Concerning the course of illness and independent living very good results were found for the rehabilitation course. Reintegration into the working process could be advanced during the stay, stagnated however after the stay. Classifying the course of rehabilitation, overall or partial success was achieved in more than 80% of the patients interviewed. The stay in a halfway house, hence, is a good possibility for medical rehabilitation of younger patients with long-term mental illness. However, it also turned out that out-patient follow-up treatment and care is of great importance for the social relationships of the often isolated patients.

Activities of Daily Living

Heterogeneity of noninvasive arrhythmic risk indicators in patients with ischemic cardiomyopathy.

Noninvasive electrocardiographic variables for arrhythmic risk stratification in chronic heart failure are of great clinical interest but remain highly controversial. This study analyzed repolarization dispersion, heart rate variability, ventricular ectopic activity, and hemodynamic parameters in 30 patients with ischemic heart failure and in 20 normal control subjects. The values for all parameters were distinctly separated between the failure and control group. Left ventricular ejection fraction had a strong relation to ventricular ectopic activity (r = .54), a weak association with repolarization dispersion (r = .29), and seemingly no parallels with heart rate variability (r = .12). However, no linear association could be detected between any of the arrhythmic risk indicators (r = .10-.22), whereas a number of linearly related angiographic-hemodynamic variables readily defined the mechanical risk profile. Thus, alterations of noninvasive arrhythmic risk indicators in heart failure are not uniform, which confounds approaches for a composite ECG risk score in individual patients.

Arrhythmias, Cardiac

Clonidine improves recovery from myocardial stunning in conscious chronically instrumented dogs.

UNLABELLED: Clonidine, an alpha2-adrenergic agonist, has been widely used in anesthesia because of its sedative, analgesic, sympatholytic, and specific hemodynamic effects. The use of clonidine in myocardial ischemia is controversial because of its bradycardic and hypotensive effects. In the present study, we tested the hypothesis that clonidine improves recovery from myocardial stunning in conscious dogs. Seven dogs were chronically instrumented to allow measurement of left atrial pressure (LAP), aortic blood pressure (ABP), left ventricular pressure (LVP), maximal rate of increase of LVP (LVdP/dtmax), and myocardial wall thickening fraction (WTF). The myocardial blood flow was measured using colored microspheres. To compensate for any potential interaction between the two ischemic episodes, experiments were performed on separate days in a cross-over fashion (four animals underwent Condition 1, and three underwent Condition 2 as their first experiment). The ischemic episodes involved 1) 10 min of ischemia of the left anterior descending (LAD) coronary artery without any intervention, and 2) 10 min of LAD ischemia 30 min after 10 microg/kg iv clonidine. WTF was measured before the induction of ischemia or the application of clonidine (baseline) and at predetermined time points until complete recovery of myocardial function. WTF recovered faster during the first 2 h of reperfusion when clonidine was administered. The increase in plasma epinephrine was attenuated by clonidine during ischemia, but there was no change during reperfusion. The increase of plasma norepinephrine levels was attenuated during ischemia and reperfusion. The hemodynamic effects of clonidine did not depress myocardial perfusion or impair myocardial function. IMPLICATIONS: In this study, we investigated the effects of IV clonidine on myocardial stunning in chronically instrumented dogs. Clonidine improved the recovery from myocardial stunning and attenuated increases in catecholamine plasma levels.

Adrenergic alpha-Agonists

Haemodynamic effects of dopexamine and nitric oxide synthase inhibition in healthy and endotoxaemic sheep.

Chronically instrumented awake healthy sheep (n = 6) received the synthetic catecholamine, dopexamine, during or without a background infusion of the nitric oxide synthase inhibitor. L-nitro-arginine-methylester (L-NAME). Three days later, hypotensive-hyperdynamic circulation was induced and maintained by continuous infusion of Salmonella typhosa endotoxin (10 ng/kg per min). After 24 h of continuous endotoxin infusion, the dopexamine L-NAME protocol was repeated. In healthy and endotoxaemic animals with and without nitric oxide synthase inhibition dopexamine caused the same haemodynamic changes: heart rate and cardiac output increased, mean arterial pressure and systemic vascular resistance decreased. L-NAME infusion induced normalisation of the hypotonic-hyperdynamic circulation in endotoxaemic animals. Dopexamine reduced some adverse effects of L-NAME treatment, like increased pulmonary vascular resistance and decreased oxygen delivery. In conclusion the haemodynamic effects of dopexamine are independent of the amount of nitric oxide production. Dopexamine may attenuate some of the adverse effects of nitric oxide synthase inhibition.

Adrenergic beta-Agonists

[Thoracic epidural anesthesia--more than an anesthesia technique].

Thoracic epidural anaesthesia (TEA) faces growing interest as an adjuvant anaesthetic and postoperative analgesic regimen. The procedure allows a specific blockade of nociceptive reflex arches and may exert beneficial effects on stress-induced alterations of organ function. Myocardial blood flow to areas at risk is improved, and paradoxical reactions of atherosclerotic coronary arteries after sympathetic stimulation are suppressed. After cardiac surgery, TEA improved postoperative recovery and resulted in better haemodynamic stability and allowed earlier extubation. During vascular surgery, the graft occlusion rate was significantly decreased. The improved pulmonary function after TEA is due to superior pain relief which allows the patients to breathe and cough sufficiently. After upper abdominal surgery, TEA leads to improved recovery of gastrointestinal function which reduces the risk of bacterial translocation. Although lumbar epidural anaesthesia is preferred by many anaesthesiologists as there is no risk of traumatizing the spinal cord, many positive effects are forgone. With insufficient rostral spread of a lumbar epidural block above the fifth thoracic level, cardiac complications can occur due to reflex activation of sympathetic outflow in unblocked thoracic regions. When the contraindications are carefully observed, TEA can be safely performed in most patients.

Anesthesia, Epidural

Effects of sympathetic nerve blockade on vasoconstrictive properties of nitric oxide synthase inhibition in sheep.

OBJECTIVE: Inhibition of nitric oxide synthase causes intense vasoconstriction. This effect is thought to be dependent on sympathetic nerve activity. Thus, we investigated the vasoconstrictive effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in sheep, in which a reversible sympathetic block was established by thoracic epidural anesthesia. METHODS: Sheep (n = 11) were surgically prepared for chronic study. After at least 5 days of recovery, L-NAME was continuously administered and hemodynamics were monitored. This was done in sheep with and without sympathetic blockade in randomized order. RESULTS: The vasoconstrictive effects of L-NAME were similar in sheep with and without sympathetic blockade. CONCLUSION: The obtained results suggest that the vasoconstrictive properties of nitric oxide synthase inhibitors are independent of sympathetic tone.

Anesthesia, Epidural

Repolarization dispersion and sudden cardiac death in patients with impaired left ventricular function.

AIMS: Prolongation of repolarization dispersion measured from the 12-lead surface ECG has been associated with sudden cardiac death and ventricular tachyarrhythmia in a variety of heart disorders. This study tested the hypothesis that increased repolarization dispersion is of prognostic value in identifying chronic heart failure patients at high risk of sudden cardiac death and ventricular tachyarrhythmia. RESULTS: In 163 patients, ischaemic (n = 126) and idiopathic dilated (n = 37) cardiomyopathy with a left ventricular ejection fraction < or = 40% were diagnosed by left ventricular angiography. During follow-up (26 +/- 15 months) 24 patients died suddenly, 10 experienced ventricular tachyarrhythmia, 19 died from pump failure, six died from acute myocardial infarction, and 97 survived. Bazett's formula rate-corrected JT-interval dispersion (JTc-d) was found to be 109 +/- 23 ms in sudden cardiac death/ventricular tachyarrhythmia patients, 57 +/- 20 ms in survivors, and 55 +/- 20 ms in patients who died from pump failure or acute myocardial infarction. Both univariate and multivariate analyses showed JTc-d to be the most important independent predictor of sudden cardiac death/ventricular tachyarrhythmia. A cut-off value of 85 ms for JTc-d had a 74% positive and a 98% negative predictive accuracy in identifying patients at risk for sudden cardiac death/ventricular tachyarrhythmia. CONCLUSION: Analysis of repolarization dispersion from the 12-lead surface ECG seems to be a useful screening method for identifying chronic heart failure patients at high risk for sudden cardiac death/ventricular tachyarrhythmia.

Angiography

The effects of thoracic epidural anesthesia on functional recovery from myocardial stunning in propofol-anesthetized dogs.

The purpose of this investigation was to examine the effects of thoracic epidural anesthesia (TEA) on myocardial stunning during propofol anesthesia. Six dogs were chronically instrumented for measurement of left atrial, aortic, and left ventricular pressure, maximal rate of increase of left ventricular pressure, and myocardial wall-thickening fraction (WTF). Myocardial blood flow was determined with colored microspheres. Experiments were performed on separate days with 1) 10 min of left anterior descending artery (LAD) ischemia during propofol anesthesia without TEA, and 2) 10 min of LAD ischemia during propofol anesthesia with TEA. WTF was measured as baseline (BL) prior to propofol anesthesia and at predetermined time points until complete recovery from stunning. Propofol anesthesia caused a significant decrease of WTF in the LAD-perfused myocardium (LAD-WTF) compared to BL in awake animals. LAD ischemia led to a further significant decrease of LAD-WTF. There were no significant differences in LAD-WTF between the two experimental conditions at any of the time points measured. TEA did not change subendocardial blood flow in nonischemic myocardium. During ischemia neither the subendocardial/subepicardial nor the occluded/normal zone blood flow ratio were affected by TEA. After myocardial ischemia during propofol anesthesia TEA does not affect functional recovery of stunned myocardium in dogs.

Anesthesia, Epidural

Multiple coronary artery-left ventricular fistulae: haemodynamic quantification by intracoronary Doppler ultrasound.

Multiple coronary artery-left ventricular fistulae involving all three major coronary arteries are extremely rare. Clinical findings are heterogeneous but include a history of typical or atypical angina pectoris in most cases. Coronary arteriography in a 65 year old woman who presented with chest pain at rest revealed multiple fine fistulae arising from the left anterior descending, left circumflex, and right coronary arteries. Left-to-left shunt was estimated by measurements of coronary artery flow velocity with intravascular Doppler ultrasound.

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